Sharon, G. et al. Specialized metabolites from the microbiome in health and disease. Cell Metab. 20, 719–730 (2014).
Google Scholar
Swann, J. R. et al. Application of 1H NMR spectroscopy to the metabolic phenotyping of rodent brain extracts: a metabonomic study of gut microbial influence on host brain metabolism. J. Pharm. Biomed. Anal. 143, 141–146 (2017).
Google Scholar
Vuong, H. E., Yano, J. M., Fung, T. C. & Hsiao, E. Y. The microbiome and host behavior. Annu. Rev. Neurosci. 40, 21–49 (2017).
Google Scholar
Needham, B. D., Kaddurah-Daouk, R. & Mazmanian, S. K. Gut microbial molecules in behavioural and neurodegenerative conditions. Nat. Rev. Neurosci. 21, 717–731 (2020).
Google Scholar
Huang, F. & Wu, X. Brain neurotransmitter modulation by gut microbiota in anxiety and depression. Front. Cell Dev. Biol. 9, 649103 (2021).
Google Scholar
Gacias, M. et al. Microbiota-driven transcriptional changes in prefrontal cortex override genetic differences in social behavior. eLife 5, e13442 (2016).
Google Scholar
Hoban, A. E. et al. Regulation of prefrontal cortex myelination by the microbiota. Transl. Psychiatry 6, e774 (2016).
Google Scholar
Hsiao, E. Y. et al. Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell 155, 1451–1463 (2013).
Google Scholar
Berer, K. et al. Commensal microbiota and myelin autoantigen cooperate to trigger autoimmune demyelination. Nature 479, 538–541 (2011).
Google Scholar
Pan, S., Mayoral, S. R., Choi, H. S., Chan, J. R. & Kheirbek, M. A. Preservation of a remote fear memory requires new myelin formation. Nat. Neurosci. 23, 487–499 (2020).
Google Scholar
Maheras, K. J. et al. Absence of claudin 11 in CNS myelin perturbs behavior and neurotransmitter levels in mice. Sci. Rep. 8, 3798 (2018).
Google Scholar
Bonnefil, V. et al. Region-specific myelin differences define behavioral consequences of chronic social defeat stress in mice. eLife 8, e40855 (2019).
Google Scholar
Galvez-Contreras, A. Y., Zarate-Lopez, D., Torres-Chavez, A. L. & Gonzalez-Perez, O. Role of oligodendrocytes and myelin in the pathophysiology of autism spectrum disorder. Brain Sci. 10, 951 (2020).
Google Scholar
Cassoli, J. S. et al. Disturbed macro-connectivity in schizophrenia linked to oligodendrocyte dysfunction: from structural findings to molecules. npj Schizophrenia 1, 15034 (2015).
Google Scholar
Needham, B. D. et al. Plasma and fecal metabolite profiles in autism spectrum disorder. Biol. Psychiatry 89, 451–462 (2020).
Google Scholar
Gamage, N. et al. Human sulfotransferases and their role in chemical metabolism. Toxicol. Sci. 90, 5–22 (2006).
Google Scholar
Chamkha, M., Garcia, J. L. & Labat, M. Metabolism of cinnamic acids by some Clostridiales and emendation of the descriptions of Clostridium aerotolerans, Clostridium celerecrescens and Clostridium xylanolyticum. Int. J. Syst. Evol. Microbiol. 51, 2105–2111 (2001).
Google Scholar
Santamaría, L., Reverón, I., Felipe, F. L. D., Rivas, B. D. L. & Muñoz, R. Ethylphenol Formation by Lactobacillus plantarum: identification of the enzyme involved in the reduction of vinylphenols. Appl. Environ. Microbiol. 84, e01064-18 (2018).
Google Scholar
Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological Profile for Cresols (CDC, 2008); https://wwwn.cdc.gov/TSP/ToxProfiles/ToxProfiles.aspx?id=946&tid=196
Penzo, M. A. et al. The paraventricular thalamus controls a central amygdala fear circuit. Nature 519, 455–459 (2015).
Google Scholar
Ahrens, S. et al. A central extended amygdala circuit that modulates anxiety. J. Neurosci. 38, 5567–5583 (2018).
Google Scholar
Duval, E. R., Javanbakht, A. & Liberzon, I. Neural circuits in anxiety and stress disorders: a focused review. Ther. Clin. Risk Manag. 11, 115–126 (2015).
Google Scholar
Robinson, O. J., Pike, A. C., Cornwell, B. & Grillon, C. The translational neural circuitry of anxiety. J. Neurol. Neurosurg. Psychiatry 90, 1353–1360 (2019).
Google Scholar
Barson, J. R., Mack, N. R. & Gao, W.-J. The paraventricular nucleus of the thalamus is an important node in the emotional processing network. Front. Behav. Neurosci. 14, 598469 (2020).
Google Scholar
Kirouac, G. J. The paraventricular nucleus of the thalamus as an integrating and relay node in the brain anxiety network. Front. Behav. Neurosci. 15, 627633 (2021).
Google Scholar
Park, H.-C. & Appel, B. Delta-notch signaling regulates oligodendrocyte specification. Development 130, 3747–3755 (2003).
Google Scholar
Wang, S. et al. Notch receptor activation inhibits oligodendrocyte differentiation. Neuron 21, 63–75 (1998).
Google Scholar
Williamson, J. M. & Lyons, D. A. Myelin Dynamics Throughout Life: An Ever-Changing Landscape? Front. Cell. Neurosci. 12, 424 (2018).
Google Scholar
Holschneider, D. P., Wang, Z. & Pang, R. D. Functional connectivity-based parcellation and connectome of cortical midline structures in the mouse: a perfusion autoradiography study. Front. Neuroinform. 8, 61 (2014).
Google Scholar
Kaller, M. S., Lazari, A., Blanco-Duque, C., Sampaio-Baptista, C. & Johansen-Berg, H. Myelin plasticity and behaviour—connecting the dots. Curr. Opin. Neurobiol. 47, 86–92 (2017).
Google Scholar
Barak, B. et al. Neuronal deletion of Gtf2i, associated with Williams syndrome, causes behavioral and myelin alterations rescuable by a remyelinating drug. Nat. Neurosci. 22, 700–708 (2019).
Google Scholar
Xie, D. et al. Clemastine improves hypomyelination in rats with hypoxic–ischemic brain injury by reducing microglia-derived IL-1β via P38 signaling pathway. J. Neuroinflammation 17, 57 (2020).
Google Scholar
Kirouac, G. J. Placing the paraventricular nucleus of the thalamus within the brain circuits that control behavior. Neurosci. Biobehav. Rev. 56, 315–329 (2015).
Google Scholar
Sharon, G., Sampson, T. R., Geschwind, D. H. & Mazmanian, S. K. The central nervous system and the gut microbiome. Cell 167, 915–932 (2016).
Google Scholar
Tian, P., Wang, G., Zhao, J., Zhang, H. & Chen, W. Bifidobacterium with the role of 5-hydroxytryptophan synthesis regulation alleviates the symptom of depression and related microbiota dysbiosis. J. Nutr. Biochem. 66, 43–51 (2019).
Google Scholar
Koyama, H. et al. Effects of housing conditions on behaviors and biochemical parameters in juvenile cynomolgus monkeys (Macaca fascicularis). Exp. Anim. 68, 195–211 (2019).
Google Scholar
Tian, J.-S. et al. A GC-MS urinary quantitative metabolomics analysis in depressed patients treated with TCM formula of Xiaoyaosan. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 1026, 227–235 (2016).
Google Scholar
Sankowski, B. et al. Higher cerebrospinal fluid to plasma ratio of p-cresol sulfate and indoxyl sulfate in patients with Parkinson’s disease. Clin. Chim. Acta 501, 165–173 (2020).
Google Scholar
Gabriele, S. et al. Urinary p-cresol is elevated in young French children with autism spectrum disorder: a replication study. Biomarkers 19, 463–470 (2014).
Google Scholar
Neul, J. L. et al. Metabolic signatures differentiate Rett syndrome from unaffected siblings. Front. Integr. Neurosci. 14, 7 (2020).
Google Scholar
Takesada, M., Miyamoto, E., Kakimoto, Y., Sano, I. & Kaneko, Z. Phenolic and indole amines in the urine of schizophrenics. Nature 207, 1199–1200 (1965).
Google Scholar
Sun, C.-Y. et al. p-Cresol sulfate caused behavior disorders and neurodegeneration in mice with unilateral nephrectomy involving oxidative stress and neuroinflammation. Int. J. Mol. Sci. 21, 6687 (2020).
Google Scholar
Franklin, K. & Paxinos, G. The Mouse Brain in Stereotaxic Coordinates (Elsevier Science, 2007).
Holdeman, L. V. & Moore, W. E. C. Anaerobe Laboratory Manual 4th edn (Virginia Polytechnic Institute and State University, 1977).
Martens, E. C., Chiang, H. C. & Gordon, J. I. Mucosal glycan foraging enhances fitness and transmission of a saccharolytic human gut bacterial symbiont. Cell Host Microbe 4, 447–457 (2008).
Google Scholar
Koropatkin, N. M., Martens, E. C., Gordon, J. I. & Smith, T. J. Starch catabolism by a prominent human gut symbiont is directed by the recognition of amylose helices. Structure 16, 1105–1115 (2008).
Google Scholar
Bolyen, E. et al. Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2. Nat. Biotechnol. 37, 852–857 (2019).
Google Scholar
Callahan, B. J. et al. DADA2: high-resolution sample inference from Illumina amplicon data. Nat. Methods 13, 581–583 (2016).
Google Scholar
Banoglu, E. & King, R. S. Sulfation of indoxyl by human and rat aryl (phenol) sulfotransferases to form indoxyl sulfate. Eur. J. Drug Metab. Pharmacokinet. 27, 135–140 (2002).
Google Scholar
Teubner, W., Meinl, W., Florian, S., Kretzschmar, M. & Glatt, H. Identification and localization of soluble sulfotransferases in the human gastrointestinal tract. Biochem. J. 404, 207–215 (2007).
Google Scholar
Sharon, G. et al. Human gut microbiota from autism spectrum disorder promote behavioral symptoms in mice. Cell 177, 1600–1618 (2019).
Google Scholar
Iadecola, C. The neurovascular unit coming of age: a journey through neurovascular coupling in health and disease. Neuron 96, 17–42 (2017).
Google Scholar
Mace, E. et al. Functional ultrasound imaging of the brain: theory and basic principles. IEEE Trans. Ultrason. Ferroelectr. Freq. Control 60, 492–506 (2013).
Google Scholar
Tiran, E. et al. Transcranial functional ultrasound imaging in freely moving awake mice and anesthetized young rats without contrast agent. Ultrasound Med. Biol. 43, 1679–1689 (2017).
Google Scholar
Needham, B. D. et al. A gut-derived metabolite alters brain activity and anxiety behaviour in mice. GitHub https://github.com/brittanyneedham/Needham_Nature2022 (2022).
Demené, C. et al. Spatiotemporal clutter filtering of ultrafast ultrasound data highly increases doppler and fultrasound sensitivity. IEEE Trans. Med. Imaging 34, 2271–2285 (2015).
Google Scholar
Osmanski, B.-F., Pezet, S., Ricobaraza, A., Lenkei, Z. & Tanter, M. Functional ultrasound imaging of intrinsic connectivity in the living rat brain with high spatiotemporal resolution. Nat. Commun. 5, 5023 (2014).
Google Scholar
Armstrong, R. A. When to use the Bonferroni correction. Ophthalmic Physiol. Opt. 34, 502–508 (2014).
Google Scholar
Holschneider, D. P., Guo, Y., Wang, Z., Vidal, M. & Scremin, O. U. Positive allosteric modulation of cholinergic receptors improves spatial learning after cortical contusion injury in mice. J. Neurotrauma 36, 2233–2245 (2019).
Google Scholar
Sokoloff, L. Localization of functional activity in the central nervous system by measurement of glucose utilization with radioactive deoxyglucose. J. Cereb. Blood Flow Metab. 1, 7–36 (1981).
Google Scholar
Wang, Z., Pang, R. D., Hernandez, M., Ocampo, M. A. & Holschneider, D. P. Anxiolytic-like effect of pregabalin on unconditioned fear in the rat: an autoradiographic brain perfusion mapping and functional connectivity study. Neuroimage 59, 4168–4188 (2012).
Google Scholar
Dobin, A. et al. STAR: ultrafast universal RNA-seq aligner. Bioinformatics 29, 15–21 (2013).
Google Scholar
Patro, R., Duggal, G., Love, M. I., Irizarry, R. A. & Kingsford, C. Salmon provides fast and bias-aware quantification of transcript expression. Nat. Methods 14, 417–419 (2017).
Google Scholar
Xu, X., Wells, A. B., O’Brien, D. R., Nehorai, A. & Dougherty, J. D. Cell type-specific expression analysis to identify putative cellular mechanisms for neurogenetic disorders. J. Neurosci. 34, 1420–1431 (2014).
Google Scholar
Zhang, Y. et al. An RNA-sequencing transcriptome and splicing database of glia, neurons, and vascular cells of the cerebral cortex. J. Neurosci. 34, 11929–11947 (2014).
Google Scholar
Zambon, A. C. et al. GO-Elite: a flexible solution for pathway and ontology over-representation. Bioinformatics 28, 2209–2210 (2012).
Google Scholar
Tyszka, J. M., Readhead, C., Bearer, E. L., Pautler, R. G. & Jacobs, R. E. Statistical diffusion tensor histology reveals regional dysmyelination effects in the shiverer mouse mutant. Neuroimage 29, 1058–1065 (2006).
Google Scholar
Mastronarde, D. N. Automated electron microscope tomography using robust prediction of specimen movements. J. Struct. Biol. 152, 36–51 (2005).
Google Scholar
Yeh, F.-C. et al. Deterministic diffusion fiber tracking improved by quantitative anisotropy. PLoS ONE 8, e80713 (2013).
Kremer, J. R., Mastronarde, D. N. & McIntosh, J. R. Computer visualization of three-dimensional image data using IMOD. J. Struct. Biol. 116, 71–76 (1996).
Google Scholar
Mastronarde, D. N. Correction for non-perpendicularity of beam and tilt axis in tomographic reconstructions with the IMOD package. J. Microsc. 230, 212–217 (2008).
Google Scholar
Carranza-Torres, I. E. et al. Organotypic culture of breast tumor explants as a multicellular system for the screening of natural compounds with antineoplastic potential. BioMed Res. Int. 2015, 618021 (2015).
Google Scholar
Leger, M. et al. Object recognition test in mice. Nat. Protoc. 8, 2531–2537 (2013).
Google Scholar
Sampson, T. R. et al. Gut microbiota regulate motor deficits and neuroinflammation in a model of Parkinson’s disease. Cell 167, 1469–1480 (2016).
Google Scholar
Komada, M., Takao, K. & Miyakawa, T. Elevated plus maze for mice. J. Vis. Exp. https://doi.org/10.3791/1088 (2008).
Takao, K. & Miyakawa, T. Light/dark transition test for mice. J. Vis. Exp. https://doi.org/10.3791/104 (2006).
Miedel, C. J., Patton, J. M., Miedel, A. N., Miedel, E. S. & Levenson, J. M. Assessment of spontaneous alternation, novel object recognition and limb clasping in transgenic mouse models of amyloid-β and Tau neuropathology. J. Vis. Exp 28, 55523 (2017).
Shih, H.-T. & Mok, H.-K. ETHOM: event-recording computer software for the study of animal behavior. Acta Zool. Taiwanica 11, 47–61 (2000).